TIS11B belongs to a group of
RNA-binding proteins (including TIS11/
tristetraprolin and TIS11D) that share characteristic tandem CCCH-type zinc-finger domains and can be rapidly induced by multiple stimuli. TIS11B has been shown to regulate
vascular endothelial growth factor (
VEGF) mRNA stability in
adrenocorticotropic hormone-stimulated primary adrenocortical cells. TIS11B has also been documented as a negative regulator of
VEGF during development, but nothing has yet been reported in the context of human
cancers. The Von Hippel-Lindau (
VHL) tumor suppressor protein regulates
VEGF gene expression at both the transcriptional and post-transcriptional levels in normoxia. However, whether it can do so in
hypoxia is still unclear. Here, we report a unique regulatory function of VHL in
VEGF expression in
hypoxia that is mediated through modulation of TIS11B
protein levels in
renal cancer cells. In normoxia, we detected increased expression of the
microRNA hsa-miR-29b in the VHL-overexpressing
renal cancer cell line 786-O. We also show that this increased expression of
hsa-miR-29b decreased TIS11B
protein expression by post-transcriptional regulation in normoxia. In contrast, in
hypoxia, increased TIS11B expression paralleled an increased TIS11B mRNA stability in VHL-overexpressing 786-O cells. This VHL-mediated TIS11B up-regulation in
hypoxia may be important for TIS11B-regulated gene expression: we observed a down-regulation of
VEGF mRNA in
hypoxia in VHL-overexpressing cells compared with parental 786-O cells, and this effect was reversible by silencing TIS11B expression.